Biomaterials Step into the 21st Century

Materials science breakthroughs are making it possible to precisely program the properties of biomaterials to make them 'bioactive.'

The use of foreign materials in the human body has an impressively long history. In approximately 600 A.D., the Mayans used mother of pearl to fashion dental implants that apparently integrated with bone. An iron dental implant dating back to 200 A.D. has been found in Europe. The use of sutures has an even longer history, stretching back some 32,000 years. Fastforwarding through the centuries, elephant ivory was used to fashion the first documented hip implant in 1891.

Most biomaterials used over the course of history were intended to be biopassive--simply tolerated by the body. This is beginning to change, however, as there is increasing demand to create biomaterials that support the field of regenerative medicine. In the meantime, inert biomaterials are also continuing to evolve.

Three Generations of Biomaterials

DSM Biomedical (Berkeley, CA) classifes inert biomaterials, which include everything from nitinol to ceramics, as the first generation of biomaterials. Such materials have traditionally been selected based on their physical properties, which should closely approximate the tissue they are meant to replace. They have also been selected for the degree to which they are biopassive and nontoxic. "In orthopedics, this type of first-generation-biomaterials thinking is best seen in total artificial joints," says William Fuller, director of business development at DSM Biomedical. "Knee and hip replacements stand out as clinical successes, since there are over one million performed annually, resulting in improved quality of life and a return to a more active lifestyle for many patients."

DSM's hails its Dyneema Purity medical fiber as "world's strongest."

There continues to be innovation among such first generation biomaterials, Fuller says, pointing to DSM's Dyneema Purity fibers as an example. Described by the company as the "world's strongest medical fiber," Dyneema Purity is being applied to cardiovascular applications such as reinforcing vascular balloon catheters. The applications of the material in the orthopedic device market is growing as well, where it appears in high-strength sutures used in rotator cuff repairs, fixation devices for ACL repair, and spine devices ranging from annulus repair to total disc replacement. The company foresees expanded use of the material in ligament fixations, in which the material's very low stretch results in a rigid fixation that can improve the chance of rapidly readhering torn ligaments to the bone.

"Ultra-high-molecular-weight polyethylene (UHMWPE) fibers are helping to move implants beyond the limitations of more-traditional orthopedic fibers and sutures," Fuller remarks. "Conventional fibers such as polyesters, polypropylene, or nylon have moderate strength and show a fairly large stretch (elongation) before they ultimately break. The UHMWPE fibers are the opposite: Their strength is much higher. On a weight basis, the fibers are more than 10 times stronger than steel, and a braid or suture made from these fibers has the potential to be twice as strong as a comparable polyester product." Elongation is practically imperceptible for this material, he adds. "When these fibers reach breaking strength, elongation is approximately 3%. These characteristics enable the design of novel, smaller medical devices."

The RxFibresorb fiber from RxFiber' is a medical-grade resorbable thermoplastic.

Innovation is also apparent in the use of materials that have a long history of use as biomaterials, comments Robert Torgerson, founder and president of RxFiber LLC (Windsor, CA; www.rxfiber.com). Take polyester, for example. "Companies developing next generation devices using polyester yarns and other biomaterials are looking at reducing the profiles of the devices," he explains. "Open surgical procedures were the norm for endovascular and vascular procedures. Now, heart valves, endovascular devices, stents, and so forth are implanted via a catheter-based system. The diameters of these delivery systems are large based on the device that needs to be delivered. This system needs to pass through an orifice, such as a femoral artery, iliac artery, or brachial artery." While this demand puts stress on the orifice, various coatings have been developed for the delivery systems to reduce this stress. "The devices are limited to particular patients that can withstand the diameter of the delivery system," Torgerson says. "A good portion of patients have small-diameter anatomies, which require smaller-diameter delivery systems. That, in turn, requires a minimal amount of biomaterials going into the delivery system to be delivered to the site."

Transcatheter endovascular devices are examples of such systems. These products now use fairly large diameter yarns in the 40-denier range requiring 20F or larger delivery systems, Torgerson notes. "To reduce the profile and maintain the integrity of the device, smaller, stronger yarns need to be developed to reduce the profile. This has led to high-tenacity polyester yarns measuring 20 denier or less with fewer filaments. This thickness maintains the integrity of the device." RxFiber has developed small-denier, high tenacity polyester yarns for such applications.

The Second Generation and Beyond

The second generation of biomaterials do more than simply aim to go unnoticed in the body. They are formulated to incorporate bioactive components, eliciting controlled actions and reactions in a physiological environment. "Prominent examples of these 'bioactive' biomaterials in the orthopedic space include injectable or implantable synthetic bone graft substitutes," Fuller explains.

Third-generation biomaterials, which are designed based on an expanded understanding of biology, aim to help achieve regeneration as opposed to repair. "Third-generation biomaterials are being designed to stimulate specific cellular responses at the molecular level," Fuller explains. "In the orthopedics space, use of bone-growth factors and platelet-rich plasma therapies signal the beginning of a larger movement toward regenerative materials that help the body heal itself. Related contemporary understanding of the molecular and cell biology of tissue healing is incorporated into materials design." Molecular modifications of polymer systems elicit specific interactions with cell surface integrins and direct cell proliferation, differentiation, and extracellular matrix production and organization, Fuller adds. "These third generation 'bio-interactive' biomaterials stimulate regeneration of living tissues. As for biocompatibility, these materials not only focus on doing no harm but are also designed as elements of the treatment itself."

Peter D. Gabriele, vice president, emerging technology at Secant Medical Inc. (Perkasie, PA) has a similar view of the future of biomaterials--stressing the importance of their use in regenerative medicine. "For the future of biomaterials to move forward, we must fully understand their consequence in the human body," he says. "Materials are not inert, and we must be smarter in making the connection between materials of construction and tissue response." Gabriele explains that the potential for biomaterials in regenerative medicine lies in developing an appropriate construct that restores an organ system back to its natural function.

"Within this context, we are dealing with two immune systems at the point of implant: the inflammatory system (the initial healing process) and the adaptive immune system (the long-term system of healing and function)," Gabriele notes. Thus, it is important to know how a material affects the immune system, the healing process, and the organ undergoing regeneration. "This intelligent design movement involves finding the compliance match not only to the material engineering properties but also to material biology, bioactivity, and biocompatibility."

Related to this trend is an uptick in R&D efforts to develop new biodegradable materials, such as polylactic acid. Capable of dissolving into lactic acid, this material can be programmed to provide structure to implants for a period of time ranging from six months to two years.

"The next-generation biodegradable polymer offers several advantages," Gabriele explains. "First, it distinguishes itself as being designable (the compliance-matching criteria can be designed in). Second, its breakdown products are metabolites, which means it doesn't produce waste that must be flushed out of the body. And finally, it is not antagonistic; it doesn't stimulate the immune system to form scar tissue."

Existing materials have a narrow window of product development capabilities, Gabriele notes. "However, the future biopolymer has a much broader window, without diminishing such benefits as compatibility and nonimmunogenic response," he adds. This single material, depending on how it is processed, will have multiple application areas. Within soft-tissue engineering, it holds the potential for use in myocardial patches, engineered blood vessels, scaffolds for cartilage restoration or retinal repair, and nerve conduits. It could also be formulated into a composite for orthopedic repair or a coating that creates a functional surface for a material.

While regenerative medicine has an exciting future, the cost of organ regeneration as the next generation of devices and biomaterials is developed should not be overlooked, remarks Torgerson from RxFiber. "This will be an extremely expensive undertaking, and there is also the time involved with the regeneration to recreate the organ of choice." However, biomaterials will still be needed to create devices for emergency situations, low-income cases, and other circumstances. "I am unsure how an aorta may be regenerated and replaced without being an open surgical procedure, he explains." But open procedures are inherently risky and potentially fatal for some patients. A transcatheter-based system using a device made of biomaterials could save time and possibly even the patient's life. "We need to continue our progress with developing next generation devices using current and next-generation biomaterials," he concludes.